In Vitro Metabolic Stability and in Vivo Biodistribution of 3-Methyl-4-furoxancarbaldehyde Using PET Imaging in Rats

详细信息    查看全文

• 作者：Adam B. Pippin ; Zaira Hidayah Mohd Arshad ; Ronald J. Voll ; Jonathon A. Nye ; Sussan Ghassabian ; Craig M. Williams ; Alessandra Mancini ; Dennis C. Liotta ; Maree T. Smith ; Mark M. Goodman
• 刊名：ACS Medicinal Chemistry Letters
• 出版年：2016
• 出版时间：June 9, 2016
• 年：2016
• 卷：7
• 期：6
• 页码：563-567
• 全文大小：355K
• 年卷期：0
• ISSN：1948-5875

文摘

Painful diabetic neuropathy (PDN) is a type of peripheral neuropathic pain that is currently difficult to treat using clinically available analgesics. Recent work suggests a progressive depletion of nitric oxide (NO) in nerve cells may be responsible for the pathobiology of PDN. The nitric oxide donor, 3-methyl-4-furoxancarbaldehyde (PRG150), has been shown to produce dose-dependent analgesia in a rat model of PDN. To gain insight into the mechanism of analgesia, methods to radiolabel PRG150 were developed to assess the in vivo biodistribution in rats. The furoxan ring was labeled with ¹³N to follow any nitric oxide release and the 3-methyl substituent was labeled with ¹¹C to track the metabolite using PET imaging. The in vitro metabolic stability of PRG150 was assessed in rat liver microsomes and compared to in vivo metabolism of the synthesized radiotracers. PET images revealed a higher uptake of ¹³N over ¹¹C radioactivity in the spinal cord. The differences in radioactive uptake could indicate that a NO release in the spinal cord and other components of the somatosensory nervous system may be responsible for the analgesic effects of PRG150 seen in the rat model of PDN.